title: Peptide-induced membrane leakage by lysine derivatives of gramicidin A in liposomes, planar bilayers, and erythrocytes.
abstract: Introducing a charged group near the N-terminus of gramicidin A (gA) is supposed to suppress its ability to form ion channels by restricting its head-to-head dimerization. The present study dealt with the activity of [Lys1]gA, [Lys3]gA, [Glu1]gA, [Glu3]gA, [Lys2]gA, and [Lys5]gA in model membrane systems (planar lipid bilayers and liposomes) and erythrocytes. In contrast to the Glu-substituted peptides, the lysine derivatives of gA caused non-specific liposomal leakage monitored by fluorescence dequenching of lipid vesicles loaded with carboxyfluorescein or other fluorescent dyes. Measurements of electrical current through a planar lipid membrane revealed formation of giant pores by Lys-substituted analogs, which depended on the presence of solvent in the bilayer lipid membrane. The efficacy of unselective pore formation in liposomes depended on the position of the lysine residue in the amino acid sequence, increasing in the row: [Lys2]gA<[Lys5]gA<[Lys1]gA<[Lys3]gA. The similar series of potency was exhibited by the Lys-substituted gA analogs in facilitating erythrocyte hemolysis, whereas the Glu-substituted analogs showed negligible hemolytic activity. Oligomerization of the Lys-substituted peptides is suggested to be involved in the process of nonselective pore formation.
authors.affiliation: A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Moscow 119991, Russia.
authors.forename: Alexandra I
authors.initials: AI
authors.lastname: Sorochkina
authors.forename: Sergei I
authors.initials: SI
authors.lastname: Kovalchuk
authors.forename: Elena O
authors.initials: EO
authors.lastname: Omarova
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Sobko
authors.forename: Elena A
authors.initials: EA
authors.lastname: Kotova
authors.forename: Yuri N
authors.initials: YN
authors.lastname: Antonenko
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects; D006096:Gramicidin / Q000737:chemistry / Q000494:pharmacology*; D008051:Lipid Bilayers; D008239:Lysine / Q000737:chemistry / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence
chemical_list: D000900:Anti-Bacterial Agents; D008051:Lipid Bilayers; D010455:Peptides; D006096:Gramicidin; D008239:Lysine
keywords: AlPcS(4); BLM; CF; Channel; DPhPC; EggPC; Erythrocyte; FCS; Gramicidin A; Leakage; Liposome; PEG; Peptide; Rh–PE; SRB; bilayer lipid membrane; carboxyfluorescein; diphytanoylphosphatidylcholine; egg yolk phosphatidylcholine; fluorescence correlation spectroscopy; gA; gramicidin A; polyethylene glycol; rhodamine–phosphatidylethanolamine; sulforhodamine; tetrasulfonated aluminum phthalocyanine